DOI: 10.1073/pnas.081620098. Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 <i>in vitro</i> and <i>in vivo</i>

Simvastatin strongly reduces levels of Alzheimer's disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo

10.1073/pnas.081620098

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Recent epidemiological studies show a strong reduction in the incidence of Alzheimer's disease in patients treated with cholesterol-lowering statins. Moreover, elevated Aβ42 levels and the ɛ4 allele of the lipid-carrier apolipoprotein E are regarded as risk factors for sporadic and familial Alzheimer's disease. Here we demonstrate that the widely used cholesterol-lowering drugs simvastatin and lovastatin reduce intracellular and extracellular levels of Aβ42 and Aβ40 peptides in primary cultures of hippocampal neurons and mixed cortical neurons. Likewise, guinea pigs treated with high doses of simvastatin showed a strong and reversible reduction of cerebral Aβ42 and Aβ40 levels in the cerebrospinal fluid and brain homogenate. These results suggest that lipids are playing an important role in the development of Alzheimer's disease. Lowered levels of Aβ42 may provide the mechanism for the observed reduced incidence of dementia in statin-treated patients and may open up avenues for therapeutic interventions.

Bibliography

Fassbender, K., Simons, M., Bergmann, C., Stroick, M., LÃ¼tjohann, D., Keller, P., Runz, H., KÃ¼hl, S., Bertsch, T., von Bergmann, K., Hennerici, M., Beyreuther, K., & Hartmann, T. (2001). Simvastatin strongly reduces levels of Alzheimerâs disease Î²-amyloid peptides AÎ²42 and AÎ²40 in vitro and in vivo. Proceedings of the National Academy of Sciences, 98(10), 5856â5861.

Authors 13

K. Fassbender (first)
M. Simons (additional)
C. Bergmann (additional)
M. Stroick (additional)
D. Lütjohann (additional)
P. Keller (additional)
H. Runz (additional)
S. Kühl (additional)
T. Bertsch (additional)
K. von Bergmann (additional)
M. Hennerici (additional)
K. Beyreuther (additional)
T. Hartmann (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:59 p.m.)
Indexed	1 month ago (Aug. 2, 2025, 12:51 a.m.)
Issued	24 years, 4 months ago (April 10, 2001)
Published	24 years, 4 months ago (April 10, 2001)
Published Online	24 years, 4 months ago (April 10, 2001)
Published Print	24 years, 3 months ago (May 8, 2001)

Funders 0

None

BibTeX

@article{Fassbender_2001, title={Simvastatin strongly reduces levels of Alzheimer’s disease β-amyloid peptides Aβ42 and Aβ40 in vitro and in vivo}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.081620098}, DOI={10.1073/pnas.081620098}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Fassbender, K. and Simons, M. and Bergmann, C. and Stroick, M. and Lütjohann, D. and Keller, P. and Runz, H. and Kühl, S. and Bertsch, T. and von Bergmann, K. and Hennerici, M. and Beyreuther, K. and Hartmann, T.}, year={2001}, month=apr, pages={5856–5861} }

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